Effects of various living-low and training-high modes with distinct training prescriptions on sea-level performance: A network meta-analysis

This study aimed to separately compare and rank the effect of various living-low and training-high (LLTH) modes on aerobic and anaerobic performances in athletes, focusing on training intensity, modality, and volume, through network meta-analysis. We systematically searched PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023. Based on the hypoxic training modality and the intensity and duration of work intervals, LLTH was divided into intermittent hypoxic exposure, continuous hypoxic training, repeated sprint training in hypoxia (RSH; work interval: 5–10 s and rest interval: approximately 30 s), interval sprint training in hypoxia (ISH; work interval: 15–30 s), short-duration high-intensity interval training (s-IHT; short work interval: 1–2 min), long-duration high-intensity interval training (l-IHT; long work interval: > 5 min), and continuous and interval training under hypoxia. A meta-analysis was conducted to determine the standardized mean differences (SMDs) among the effects of various hypoxic interventions on aerobic and anaerobic performances. From 2,072 originally identified titles, 56 studies were included in the analysis. The pooled data from 53 studies showed that only l-IHT (SMDs: 0.78 [95% credible interval; CrI, 0.52–1.05]) and RSH (SMDs: 0.30 [95% CrI, 0.10–0.50]) compared with normoxic training effectively improved athletes’ aerobic performance. Furthermore, the pooled data from 29 studies revealed that active intermittent hypoxic training compared with normoxic training can effectively improve anaerobic performance, with SMDs ranging from 0.97 (95% CrI, 0.12–1.81) for l-IHT to 0.32 (95% CrI, 0.05–0.59) for RSH. When adopting a program for LLTH, sufficient duration and work intensity intervals are key to achieving optimal improvements in athletes’ overall performance, regardless of the potential improvement in aerobic or anaerobic performance. Nevertheless, it is essential to acknowledge that this study incorporated merely one study on the improvement of anaerobic performance by l-IHT, undermining the credibility of the results. Accordingly, more related studies are needed in the future to provide evidence-based support. It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.


Introduction
The hypoxic training techniques of "Live High-Train High" (LHTH) and "Live High-Train Low" (LHTL), which necessitate athletes to spend daily prolonged durations in high altitudes, have been used for over half of a century [1,2].This camp-style hypoxic technique is often employed by individual and team-sport athletes during the pre-season training phase to gain a competitive edge.However, research has suggested that such long-term hypoxic exposure training can potentially cause a range of detrimental effects in athletes (such as muscle cell deterioration and immunological disruptions etc.) [3][4][5][6][7][8].In recent years, with the evolution of hypoxia equipment and to mitigate the drawbacks associated with chronic hypoxia [9], most studies have focused on LLTH modes that expose athletes to only discrete hypoxia during specific training or rest periods [10][11][12].Recent reviews have introduced updated panorama for hypoxia training [13,14] and divided LLTH into two major categories (active and passive) based on the parameters of the training regimen.The passive hypoxic paradigm is intermittent hypoxic exposure (IHE), where athletes are exposed to short (<3 hours) yet intense passive hypoxia during rest periods [15].The active hypoxic paradigm encompasses continuous hypoxia training (CHT), which is a moderate-intensity training that lasts for approximately 30 minutes [16], and intermittent (moderate-high intensity) hypoxia training.According to the training duration and ratio of work to rest, intermittent training can be divided into repeated sprint training in hypoxia (RSH; work interval: 5-10 s and rest interval: approximately 30 s) [17], interval sprint training in hypoxia (ISH; work interval: 15-30 s) [18], high-intensity interval training (IHT; short duration: 1-2 min [19] and long duration: > 5 min [20]).In addition, some studies have combined continuous and intermittent hypoxia training aimed at optimizing aerobic and anaerobic capabilities concurrently [21][22][23].
Current literature has suggested that LLTH variants cannot trigger adequate hypoxic stimuli to induce related hematological alterations [24][25][26].The associated primary mechanism is to induce muscular and peripheral adaptations [15,27] by adding extra hypoxic load during training.However, the ongoing discourse about the effectiveness of various LLTH variants remains unresolved [28][29][30][31].Critics argue that restriction of oxygen availability could substantially decrease absolute training intensity [31,32].This could potentially induce degenerative changes, subsequently limiting the enhancement of sea-level performance.The first meta-analysis conducted by Bonetti and Hopkins (2009) on hypoxic training suggested that compared with normoxic training, LLTH does not significantly enhance athletes' performance.However, some perspectives have highlighted that previous studies did not consider the potential impact of variable training prescriptions [10,14].Recent meta-analyses have also suggested that high-intensity interval training [33] or repeated sprint training [34] in a hypoxic condition can effectively improve performance or aerobic capacity in athletes.Training at different duration and intensities has been shown to place diverse physiological demands on the body, leading to potential differences in subsequent adaptive changes, irrespective of whether the environment is normoxic or hypoxic [28,35].Hence, discerning the disparities in performance outcomes across diverse training modalities of LLTH is crucial for its practical application.
Compared with the usual meta-analysis used in previous studies, network meta-analysis (NMA) can generate a clear hierarchy between various interventions by synthesizing the results of direct and indirect comparisons to derive more comprehensive and definitive comparison results [36,37].Therefore, LLTH variants were meticulously divided based on their various training parameters.Subsequently, we conducted an NMA to comprehensively compare and rank the performance (i.e., aerobic and anaerobic) enhancement effects of various hypoxic training modes in athletes.

Methods
This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses NMA (S1 Checklist and S1 File) [38].Additionally, the study protocol has been registered with PROSPERO under registration number CRD42023421683.

Data source and search
The following English electronic databases were searched systematically: PubMed, Web of Science, Embase, EBSCO, and Cochrane from their inception date to June 30, 2023.The following search syntax was utilized: ("altitude" OR "hypoxia") AND ("high-intensity interval training" OR "repeated sprint training" OR "interval sprint training" OR "continuous training" OR "intermittent exposure" OR "performance") (S1 Table ).we manually searched all review articles related to altitude or hypoxic training and traced additional possible studies by reviewing their reference lists.

Study selection
The standards were based on the PICOS approach (participants, interventions, comparators, outcomes, and study design).The participants were athletes who had received training but had not been exposed to hypoxia in the last 6 months.There were no criteria regarding the sport type and training level of the participants (youth teams, university teams, national teams, professional club teams, etc.).We categorized LLTH into seven modes based on the training type, intensity, and volume (duration of work interval) (for detailed classification and definition, see Fig 1 1).All the training plans for the control group are implemented in a normoxic environment.In the face-to-face studies included in the selected systematic reviews, the comparator should be any of the seven hypoxic modes.At least one test result of interest should have been obtained in the study.The results were mainly divided into

Data extraction and quality evaluation
All relevant articles retrieved from the aforementioned electronic databases were stored in EndNote X9 reference manager, and three investigators reviewed and selected the retrieved articles based on the aforementioned reference criteria.Subsequently, relevant data was extracted from the qualified articles.2).The hypoxic dosage between different hypoxic types was coordinated using the "kilometer hours" model [39].The dosage model was defined as km�h = (m/1000)× h ("m" represents the altitude of the exposure environment; "h" represents the total exposure duration).The methodological quality of the Included articles was evaluated by two independent reviewers using the Physiotherapy Evidence Database (PEDro) scale [40].The PEDro scale includes 11 items made up of three items from the Jadad scale and nine items from the Delphi list.The PEDro scale score for randomized controlled trials ranges from 0 (low quality) to 10 (high quality), and a score of �6 represents high-quality research.The first item on the PEDro scale (eligibility criteria specified) is used to establish external validity; thus, the score is not included in the total score.Any disagreement during the above process was resolved by a review group within the team (HY, YH, TS and XM) through consensus and arbitration.

Statistical analysis
We used the R software (version 3.6.3)package netmeta (www.rproject.org)to perform the NMA, combining direct and indirect comparisons in a frequency model [41,42].The standardized mean difference (SMD) and 95% credible interval (CI) was used as effect size indicators.We used the random effects NMA model to collate the size of the study effect.The circle size in the network evidence graph represents the sample size, and the lines between the circles   we performed indirect comparisons using NMA.In addition, the SMD and 95% CI of all paired comparisons are reported, and the effect of each physical activity intervention on maximal oxygen uptake compared with that observed in the control group is reported in a league table using a forest plot.We ranked the types of physical activities using P scores based on the degree of improvement in maximal oxygen uptake among athletes.The P score ranges from 0 to 1, with a higher score indicating a greater improvement in aerobic capacity [43].We used the tau squared (τ 2 ) test and p-value to qualitatively analyze heterogeneity between the studies [44,45].The larger the τ 2 and the smaller the p-value, the bigger the heterogeneity.Conversely, the smaller the τ 2 and the bigger the p-value, the smaller the heterogeneity.In addition, we used I 2 , which is distributed between 0% and 100%, to quantitatively analyze the heterogeneity between the study results.An I 2 less than 25% indicated low heterogeneity, ranging from 25% to 50% indicated medium heterogeneity; and >75% indicated high heterogeneity.Therefore, when I 2 was >50%, the heterogeneity was significant.We used global and local methods to test for inconsistency in the study results.For global inconsistency, we used the design-by-treatment test to evaluate inconsistency [46].In addition, we used the node-splitting method in the R netmeta package for the local inconsistency test [47].We conducted network meta-regression analysis using the R gemtc package to analyze potential sources of heterogeneity (publication year, sample size, mean age, percent male, exercise duration, exercise frequency, and total time per session).We compared adjusted funnel plots to evaluate the risk of publication bias under specific circumstances.Additionally, we analyzed the funnel plots using the Egger method.A p<0.05 indicated publication bias.We evaluated the sensitivity of our study by repeating each NMA after excluding studies with high risk of bias.

Study characteristics and quality assessment
The search process of the systematic reviews is shown in Fig 1 .After excluding 2,292 reports based on the title and abstract, 444 full-text articles were retrieved.During the examination of the full texts, we selected and included 56 studies with interesting results (the citations included studies are provided in S3 Table ).A total of 1,040 participants, most of whom were male (n = 964/92.69%),were included in the 56 studies.Additionally, most participants were endurance athletes (n = 770/74.04%).All the participants in the included studies, except two who were boxing and tennis players, were team-sports athletes (n = 270/25.96%).The sample size for the studies ranged from 4 to 25.The training period ranged from 5 to 56 days (average, 28.9 days, standard deviation [SD] = 13.214), and the weekly exercise training frequency ranged from 2 to 7 (average frequency, 3.44, SD = 1.67).The specific parameters of the training programs in each study are shown in Table 2 (the scoring details per study are provided in S2 Table ).The PEDro scale was used to determine the quality of the included study, with results showing an average score of 6.327±1.203and indicating a generally high methodological quality.Only three studies had scores below the predetermined threshold of 5 points.

Network meta-analysis
Aerobic performance.The league plot (Table 3) results showed that l-IHT can improve an athlete's aerobic performance better than all the other hypoxic modes, with an SMD ranging from 0.49 and 0.78.The I 2 value for aerobic performance was 8% (low heterogeneity).The global Q score for inconsistency was 0.55 with a p-value of 0.6774 (Statistical methods in details, evaluation of heterogeneity and inconsistency in S5 and S6 Files).improvements in anaerobic performance, with SMDs (95% CrI) ranging from 0.97 (0.12-1.81) for l-IHT to 0.32 (0.05-0.59) for RSH, and l-IHT ranks first with a P-score of 0.95 (Fig 5).In addition, the NMA results (Table 4) showed that all intermittent hypoxic training could improve anaerobic performance better than continuous and interval training under hypoxia and normoxic training.However, it should be noted that this study only included one study  on the improvement of anaerobic performance by l-IHT.The I 2 value for anaerobic performance was 20.5% (low heterogeneity).The global Q score for inconsistency was 0.14 with a pvalue of 0.7037 (Statistical methods in details, evaluation of heterogeneity and inconsistency in S5 and S6 Files).

Discussion
This study classified LLTH into several specialized hypoxic modes according to the type, intensity, and volume of training prescription and subsequently used NMA to comprehensively compare and rank the effects of the various hypoxic modes on athletes' aerobic and anaerobic performances.The results showed that only active intermittent hypoxic modes (l-IHT, s-IHT, RSH, and ISH) compared with normoxic training were effective in improving athletes' performance.Of these, for both aerobic and anaerobic performances, l-IHT with a high volume (longer duration of training interval) and intensity showed the best results.It seems difficult to achieve beneficial adaptive changes in performance with intermittent passive hypoxic exposure and continuous low-intensity hypoxic training.The pooled data indicates that among various LLTH modes, only intermittent modes with high-intensity and large-volume training had significant large effects on enhancing aerobic performance.The findings substantiate the perspective that high intensity is integral to enhancing an athlete's endurance during hypoxic training [10,15,35].In a hypoxic environment, the diminished oxygen content inevitably affects arterial oxygen pressure (SaO 2 ), reducing oxygen availability to muscle and brain tissues and constraining aerobic metabolic function [48].Such physiological responses could notably impair performances during training with high aerobic components [49][50][51].Additionally, it has been confirmed that high-level  athletes are likely to encounter greater impairments [52,53].Absolute exercise intensity in the hypoxic group that is not only markedly lower than the normoxic group but also falls short of the threshold that could invoke beneficial adaptations is observed when CHT, requiring a relatively lesser intensity, is implemented [10,54].Conversely, matching a higher training intensity (VT2/anaerobic threshold/80% VO 2 max) during intermittent hypoxia training can mobilize a larger proportion of anaerobic metabolism to participate in energy supply [55], limiting the decrease in absolute exercise intensity [56].Presently, it is understood that CHT exhibits a strong correlation with the amplification of aerobic performance and metabolic adaptations in active muscles.Hypoxic training with adequate intensity may enhance muscle oxidative capacity by optimizing substrate selection and augmenting mitochondrial function [57][58][59].As high-intensity training continues, a large amount of lactic acid gradually accumulates in the tissues, which strongly stimulates the buffering capacity of the muscles [27].Previous reports have indicated that after high-intensity hypoxic training, compared with normoxic training, the monocarboxylate transporter (MCT-1/4) related to H+ management shows significant adaptive changes [23,60,61], and the density of the capillaries in the working muscles (the ratio of muscle fibers to capillaries) also increases significantly [54,62].
In addition to high intensity, longer work-interval duration (higher volume of training and hypoxic dose) is closely related to the improvement of endurance and aerobic capability [63][64][65][66].Our results support this hypothesis, as both ISH and s-IHT did not show superiority over normoxic training.Adequate training volume cannot only pose greater challenge to aerobic metabolism and pH regulation but can also trigger special adaptations with more hypoxic dose application.A decrease in tissue Fraction of Inspired Oxygen (FiO 2 ) catalyzes the accumulation of Hypoxia-Inducible Factor 1 (HIF-1) [67][68][69], a transcription factor that decays rapidly in normoxic environments [70].This transcription factor has been validated to effectively activate regulatory factors related to the aforementioned metabolic adaptations [71,72].Furthermore, after high-intensity hypoxic training, various adaptation mechanisms closely related to aerobic performance (such as myoglobin concentration, citrate synthase, exercise economy, etc.) have been widely reported [9,59,73,74].Moreover, several studies have enhanced the comprehension of these physiological adaptations following l-IHT by evaluating related mRNA [9,72,75].However, no studies have directly explored the impact of specific training variables (intensity and volume) on the amplification of aerobic performance in athletes during hypoxic training.
Beyond training intensity and volume, the degree of hypoxia is also a significantly vital element of training prescription.Studies on acute hypoxia have evidenced that exposure to moderate altitudes significantly impairs SaO 2 and disturb dynamic balance [76].The degree of stimulation increases with increasing altitude [77].However, Karayigit et al. (2022) conducted separate investigations into the acute impacts of moderate and high hypoxia levels on the high-intensity intermittent performance of athletes.The studies revealed no substantial differences between both conditions, and no significant detriments were observed compared with that observed in the normoxic group.Additionally, Warnier et al.'s research found no notable variation in performance enhancement (measured according to incremental test results) across the 2000 m, 3000 m, and 4000 m hypoxic groups following a six-week course of hypoxia training [78].However, given the scarcity of studies and small sample size, these findings are insufficient to conclusively assert any uniform impact of varied hypoxia levels in high-intensity training on athletes' aerobic capacity.Finally, the physiological responses and adaptations post-hypoxia demonstrate discernible individual variations, which cannot be ignored [53].Several studies have indicated that elite athletes, compared with athletes at the lower training levels, endure more significant damage in hypoxic conditions, primarily due to the restrictions in pulmonary gas exchange [52].This finding is corroborated by the strong correlation between sea-level and hypoxic VO 2 max [79].While the oxidative capacity of elite athletes may have reached its limit after extensive years of training, Ponsot et al. reported that post-IHT, the skeletal muscles of high-level athletes exhibit qualitative adaptation (increased Km for ADP) rather than a quantitative one [58].These adaptations can contribute to improved endurance performance through the better integration of energy demand and utilization.This re-emphasizes that, especially for elite athletes with extended years of training experience, sufficient duration of work intervals is the key to enhancing aerobic performance.This is the first study attempting to explore the impact of various LLTH variants on athletes' anaerobic performance using meta-analysis.The results show that all active intermittent hypoxic modes compared with normoxic training can effectively improve athletes' anaerobic performance.Further, Although the results demonstrated that hypoxic training with highintensity and long-duration working interval (l-IHT) has the best improvement effect on anaerobic performance [19], it is regrettable that this study only included one related research, which greatly reduced the statistical power and result credibility.As highlighted, athletes striving to match the same external work rate (absolute exercise intensity) under hypoxic conditions, equivalent to normoxic conditions, require the considerate use of anaerobic metabolism for energy.The training intensity executed directly correlates with the stimulation of anaerobic metabolism-the higher the intensity, the greater the stimulation, and the longer the duration, the more profound the buffering capacity stimulation.Studies on IHT indicate significant correlation between enhancement of anaerobic performance and adaptation of glycolytic enzyme capacity (phosphofructokinase) [63,65,80], MCT-1/4 [23], and capillary density.Moreover, the current literature substantiates that moderate acute hypoxia does not curtail athletes' anaerobic function [81].A noticeable but substantial reduction in resting SaO 2 , from 95% to 92%, occurs when athletes train above sea level (ambient PIO 2 = 159 mmHg) to a moderate altitude (3000 m, ambient PIO 2 = 110 mmHg).The situation intensifies at higher altitudes (5000 m, ambient PIO 2 = 85 mmHg), where SaO 2 plummets to 80% or lower [32].The significant decrease in SaO 2 implies greater demand for and stimulation of anaerobic metabolism.Nevertheless, caution is needed as the more severe the hypoxia, the greater the interference with autonomic nervous system activity [82,83], leading to the accumulation of fatigue and stress.Therefore, the real-time monitoring of physiological characteristics and training intensity is vital in ensuring the successful execution of hypoxia training.Czuba et al. (2017) highlighted the essential role of supplementary strength training in enhancing anaerobic performance.Some studies have suggested that hypoxic exposure can have harmful effects on muscle tissue, reducing protein synthesis [54,84,85] and leading to muscle fiber atrophy.However, short-term hypoxic exposure, particularly when combined with resistance training, could have a reverse effect through the stimulation of muscle protein synthesis [86,87], which is beneficial for improving anaerobic performance.
Interestingly, the combination of both continuous and intermittent training in a hypoxic condition has not shown significant enhancement in either aerobic or anaerobic performances.This type of combined hypoxia regimen can be divided into two as follows: 1) continuous and intermittent training sessions that are performed separately each week [22,88,89] and 2) continuous and intermittent training conducted during a session [21,23,90,91].The result of comprehensive data indicates that engaging in additional continuous low-intensity training under hypoxia will not produce additional effects and may even deepen fatigue.The significant effects shown by some combined hypoxia programs may also be due to the contribution of high-intensity intermittent training sessions.Pure passive hypoxic exposure compared with IHE has not shown any enhanced effect on athletic performance, which is consistent with most reviews.Our recent study also proves that IHE cannot improve the maximum oxygen uptake of athletes [15,30,92,93].Finally, it is worth mentioning that, apart from l-IHT, RSH is the only hypoxic technique that can simultaneously improve aerobic and anaerobic performances (though marginally).Compared with intermittent hypoxic training, RSH has shorter but more intense work intervals with insufficient recovery in between workouts [28].This insufficiency stimulates special physiological reactions among athletes after an RSH intervention, with type II muscle fibers displaying greater degree of recruitment and oxygenation capabilities [28,34].The correlation between oxidative tendencies (a non-hematological central and peripheral mechanisms) in fast muscle fibers and the enhancement in aerobic and anaerobic performance presents a noticeable trend [17,94,95].Nonetheless, several studies emphatically assert that athletes' VO2max and endurance test results did not improve subsequent to RSH [34,[96][97][98], but it is noteworthy that Galvin et al. proposed that the amplifying impact of RSH on anaerobic or aerobic performance is closely related to the work-rest ratio [17].Nevertheless, the marginal enhancement of both aerobic and anaerobic performance may merely constitute supplementary advantages of RSH.In practical application, the primary aim of RSH is to bolster the repeated sprint ability (mixed-oxide metabolism) of team or racquet-sports athletes [28,34,92].

Limitations
While this study confirms an impact of LLTH on aerobic and anaerobic performance based on the intensity, volume, and type of hypoxic training, several confounding factorsunquantifiable in this study-might affect the study outcomes.These include the degree of hypoxia, the integration of additional normoxic training, training frequency, and overall session volume.The effect of these particular arrangements on real-world applications is significant and necessitates further investigation.Furthermore, the characteristics of the research population are specific to males, as they were the majority (92.69%).Some studies have postulated that females exhibit lower SaO 2 sensitivity to hypoxic stimuli than that observed in males [99,100], insinuating minimal impact of hypoxic training on female athletes' performance.Consequently, we cannot definitively determine whether our conclusions are applicable to female athletes.Although some reports have suggested that female athletes can benefit from hypoxic training, the overall sample size is substantially small, and the statistical power of the results is relatively weak.Besides gender, other characteristics such as the sports athletes participate in and their competitive levels are also worthy of further investigation.Unfortunately, the current number of studies included does not support conducting methods like subgroup analysis (after grouping by characteristics, the limited number of studies would severely compromise the credibility of the outcomes and the network connectivity of meta-analysis).
Finally, it is important to note that while the results indicated that l-IHT had the most significant impact on enhancing anaerobic performance, these findings should not be regarded as conclusive due to the small number of pertinent studies analyzed.Further research is necessary to investigate the effects of interval hypoxic training with longer work durations on anaerobic performance, which is vital for the effective practical implementation of hypoxic technique.

Conclusion
Among the various LLTH strategies, only active intermittent hypoxic modes compared with normoxic training have shown significant enhancements of athletic performance.Intermittent hypoxic training with adequate work-interval durations demonstrated the most advantageous effects on aerobic performances.Neither IHE nor CHT was proven effective.

8 Julian
Fig 2 displays a network diagram of the qualified aerobic performance comparisons; all hypoxic training methods were compared with normoxic training at least once.A total of 53 studies reported changes in their primary outcome, aerobic performance among 1,021 participants (98.17%).The forest plot (Fig 3) shows that only l-IHT and

Fig 4
Fig 4 shows the network graph of anaerobic performance comparisons, where only RSH and ISH were directly compared.29 studies reported changes in anaerobic performance in the main results of 568 participants (54.62%).Compared with conventional oxygen training, all intermittent hypoxia training methods (l-IHT, ISH, s-IHT, and RSH) showed significant

Fig 2 .
Fig 2. Network plot of aerobic performance.The size of the nodes corresponds to the number of participants randomized to each hypoxic training.Exercise type with direct comparisons are linked with a line; its thickness corresponds to the number of trials evaluating the comparison.IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term high-intensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group (normoxic training)".https://doi.org/10.1371/journal.pone.0297007.g002

Fig 3 .
Fig 3. Forest plot change in effect of aerobic performance.Various LLTH modes are ranked according to the surface under the curved cumulative ranking probabilities.Treatments crossing the y-axis are not signifcantly diferent from CON.The n value represents the number of studies that were directly compared to the control group.SMD "standardized Mean Diference"; CrI "Credible Interval"; IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term high-intensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group".https://doi.org/10.1371/journal.pone.0297007.g003

Fig 4 .
Fig 4. Network plot of anaerobic performance.The size of the nodes corresponds to the number of participants randomized to each hypoxic training.Exercise type with direct comparisons are linked with a line; its thickness corresponds to the number of trials evaluating the comparison.IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term high-intensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group (normoxic training)".https://doi.org/10.1371/journal.pone.0297007.g004

Fig 5 .
Fig 5. Forest plot change in effect of anaerobic performance.Various LLTH modes are ranked according to the surface under the curved cumulative ranking probabilities.Treatments crossing the y-axis are not signifcantly diferent from CON.The n value represents the number of studies that were directly compared to the control group.SMD "standardized Mean Diference"; CrI "Credible Interval"; IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term highintensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group (normoxic training)".https://doi.org/10.1371/journal.pone.0297007.g005 and Table 1 in S2 File) (Table

Table 1 . Definition of LLTH modes. Hypoxic training mode Definition
to the metabolic characteristics in the test: aerobic and anaerobic performances.The reference indicators for aerobic and anaerobic performances include some test results that have been proven to be highly correlated.We have chosen the Incremental Treadmill Test (Time to exhaustion (min) etc.), 3 min All-Out Test (average power output (W) etc.), YYIR test level I and II (Ddistance Covered (m)), Run test (distance � 1000 m; duration (sec- (30 repetition of several short "all-out" exercise bouts (�15 s) in hypoxia interspersed with incomplete recoveries(30s, exercise-to-rest ratio <1:4) intermittent exposure to a severe hypoxia during rest 1) Alternatively receiving normoxia and hypoxia exposure 2) Persistently receiving hypoxia exposure https://doi.org/10.1371/journal.pone.0297007.t001two categories according analysis of studies on various types of hypoxic and normoxic training.We excluded studies on a single exercise in an acute hypoxia condition.In addition, studies that included special training interventions (i.e., cold, hot, or humid environments, blood flow restriction intervention, etc.) or special nutritional supplements (i.e., nitrate, caffeine, etc.) were excluded.

Table 2 .
(Continued) ://doi.org/10.1371/journal.pone.0297007.t002represent direct comparisons between two types of physical activities or interventions.The width of the connecting line reflects the number of studies that directly compared the two interventions.If no connecting line is established between the two types of physical activities, experiment"; UCT "unrandomized control experiment"; f "female"; m "male"; IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term high-intensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group (normoxic training)"; PPO "peak power output"; APO "average power output"; RSA "repeated sprint ability"; YYIR test "The Yo-Yo Intermittent Recovery Test"; N "normoxic group", H "hypoxic group".https

Table 3 . League table for changes in aerobic performance associated with various LLTH modes.
presented in the form of SMD (95% CrI).various LLTH modes are ranked according to the surface under the curve cumulative for overall effect starting with the best from left to right.The results of the network metaanalysis are showed in the lower left part, and results from pairwise comparisons in the upper right half (if available).Cells shown in bold indicate signifcant results.IHE "intermittent hypoxic exposure"; CHT "continuous hypoxic training"; RSH "Repeated sprint training in hypoxia"; ISH "Interval sprint training in hypoxia"; s-IHT "Short-trem high-intensity Interval training"; l-IHT "Long-term high-intensity interval training"; C+I "Continuous and Interval training under Hypoxia"; CON "control group (normoxic training)".https://doi.org/10.1371/journal.pone.0297007.t003